Cellular Imaging and Biophysics

Structural Cell Biology

Macromolecular crystallography, in combination with other biophysical and biochemical techniques, is the most powerful tool currently available for obtaining the high resolution information necessary to understand the details of the macromolecular interactions governing cell life. Shortly after research groups within the department identify which interactions are important, efforts to visualize critical macromolecular complexes begin.

One group of current projects focuses on understanding protein-RNA interactions, as required for RNA processing; another aims to understand the last steps of exocytosis at the atomic level.

Cellular Imaging

We are seeing a revolution in imaging, the revolution is seeing. Progress in cell biology is closely linked with advances in microscopy.

Indeed, our understanding of how cells work is intimately tied to the tools that allow us to "see" them and their components in space and time. Our department has a long history of applying state-of-the-art microscopy to understand basic cell biological processes. In fact, the Yale department of Cell Biology was created by Nobel laureate Dr. George Palade, a pioneer in the use of electron microscopy to examine the ultrastructural organization of cells. Our tradition of using imaging to discover and understand complex cellular phenomenon remains in the fore.

In particular in the last decade, with the development of green fluorescent protein (GFP) and rainbow of multicolored probes it is now possible to specifically label virtually any molecule and directly probe its function in live cells by light microscopy. This ability to visualize, often for the first time, the dynamics of proteins in vesicles, organelles, cells and tissue has begun to provide new insights into how cells function in health and disease. Such work yield unique mechanistic insight by directly illustrating the complex spatial-temporal dynamics of fundamental cellular processes studied by many labs here including: mitosis, morphogenesis, polarization, T cell recognition, embryonic development, membrane trafficking, and cytoskeleton dynamics.

Many of these processes are highly dynamic and are challenging to image by traditional means. In this aim, we are strongly committed to the development and application of new optical imaging methods that will enable us and others to understand the complex organization within and between cells. For instance, powerful optical techniques like Total Internal Reflection Fluorescent Microscopy (TIRFM) and Fluorescence Correlation Spectroscopy (FCS) allow us to essentially do biochemistry at the single vesicle and molecule level inside cells. Similarly, we are applying 4D multicolor confocal imaging and reconstruction to understand the dynamic organization of cells and tissue - and ultimately how it's altered in human disease. Importantly to our continued progress, a new 'CINEMA' imaging center (Cellular Imaging using New Microscopy Approaches) was recently created and has close corporate partnerships so as to provide a platform to test, develop and apply new imaging instrumentation.

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